title: Designed iron carbonyls as carbon monoxide (CO) releasing molecules: rapid CO release and delivery to myoglobin in aqueous buffer, and vasorelaxation of mouse aorta.
abstract: The physiological roles of CO in neurotransmission, vasorelaxation, and cytoprotective activities have raised interest in the design and syntheses of CO-releasing materials (CORMs) that could be employed to modulate such biological pathways. Three iron-based CORMs, namely, [(PaPy(3))Fe(CO)](ClO(4)) (1), [(SBPy(3))Fe(CO)](BF(4))(2) (2), and [(Tpmen)Fe(CO)](ClO(4))(2) (3), derived from designed polypyridyl ligands have been synthesized and characterized by spectroscopy and X-ray crystallography. In these three Fe(II) carbonyls, the CO is trans to a carboxamido-N (in 1), an imine-N (in 2), and a tertiary amine-N (in 3), respectively. This structural feature has been correlated to the strength of the Fe-CO bond. The CO-releasing properties of all three carbonyls have been studied in various solvents under different experimental conditions. Rapid release of CO is observed with 2 and 3 upon dissolution in both aqueous and nonaqueous media in the presence and absence of dioxygen. With 1, CO release is observed only under aerobic conditions, and the final product is an oxo-bridged diiron species while with 2 and 3, the solvent bound [(L)Fe(CO)](2+) (where L = SBPy(3) or Tpmen) results upon loss of CO under both aerobic and anaerobic conditions. The apparent rates of CO loss by these CORMs are comparable to other CORMs such as [Ru(glycine)(CO)(3)Cl] reported recently. Facile delivery of CO to reduced myoglobin has been observed with both 2 and 3. In tissue bath experiments, 2 and 3 exhibit rapid vasorelaxation of mouse aorta muscle rings. Although the relaxation effect is not inhibited by the soluble guanylate cyclase inhibitor ODQ, significant inhibition is observed with the BK(Ca) channel blocker iberiotoxin.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA.
authors.forename: Margarita A
authors.initials: MA
authors.lastname: Gonzalez
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Fry
authors.forename: Richard
authors.initials: R
authors.lastname: Burt
authors.forename: Riddhi
authors.initials: R
authors.lastname: Davda
authors.forename: Adrian
authors.initials: A
authors.lastname: Hobbs
authors.forename: Pradip K
authors.initials: PK
authors.lastname: Mascharak
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects*; D002248:Carbon Monoxide / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D005296:Ferrous Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006321:Heart; D006736:Horses; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D009211:Myoglobin / Q000737:chemistry / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects; D014867:Water / Q000737:chemistry
chemical_list: D005296:Ferrous Compounds; D009211:Myoglobin; D014867:Water; D002248:Carbon Monoxide